TY  - JOUR
A1  - Mumcuoglu, Didem
A1  - Siverino, Claudia
A1  - Tabisz, Barbara
A1  - Kluijtmans, Bas
A1  - Nickel, Joachim
T1  - How to use BMP-2 for clinical applications? A review on pros and cons of existing delivery strategies
JF  - Journal of Translational Science
N2  - No abstract available.
KW  - BMP-2
KW  - clinical applications
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158678
VL  - 3
IS  - 5
ER  - 
TY  - JOUR
A1  - Siverino, Claudia
A1  - Fahmy-Garcia, Shorouk
A1  - Mumcuoglu, Didem
A1  - Oberwinkler, Heike
A1  - Muehlemann, Markus
A1  - Mueller, Thomas
A1  - Farrell, Eric
A1  - van Osch, Gerjo J. V. M.
A1  - Nickel, Joachim
T1  - Site-directed immobilization of an engineered bone morphogenetic protein 2 (BMP2) variant to collagen-based microspheres induces bone formation in vivo
JF  - International Journal of Molecular Sciences
N2  - For the treatment of large bone defects, the commonly used technique of autologous bone grafting presents several drawbacks and limitations. With the discovery of the bone-inducing capabilities of bone morphogenetic protein 2 (BMP2), several delivery techniques were developed and translated to clinical applications. Implantation of scaffolds containing adsorbed BMP2 showed promising results. However, off-label use of this protein-scaffold combination caused severe complications due to an uncontrolled release of the growth factor, which has to be applied in supraphysiological doses in order to induce bone formation. Here, we propose an alternative strategy that focuses on the covalent immobilization of an engineered BMP2 variant to biocompatible scaffolds. The new BMP2 variant harbors an artificial amino acid with a specific functional group, allowing a site-directed covalent scaffold functionalization. The introduced artificial amino acid does not alter BMP2′s bioactivity in vitro. When applied in vivo, the covalently coupled BMP2 variant induces the formation of bone tissue characterized by a structurally different morphology compared to that induced by the same scaffold containing ab-/adsorbed wild-type BMP2. Our results clearly show that this innovative technique comprises translational potential for the development of novel osteoinductive materials, improving safety for patients and reducing costs.
KW  - bone morphogenetic protein 2 (BMP2)
KW  - bone regeneration
KW  - covalent coupling
KW  - subcutaneous animal model
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284572
SN  - 1422-0067
VL  - 23
IS  - 7
ER  - 
TY  - JOUR
A1  - Fahmy-Garcia, Shorouk
A1  - Farrell, Eric
A1  - Witte-Bouma, Janneke
A1  - Robbesom-van den Berge, Iris
A1  - Suarez, Melva
A1  - Mumcuoglu, Didem
A1  - Walles, Heike
A1  - Kluijtmans, Sebastiaan G. J. M.
A1  - van der Eerden, Bram C. J.
A1  - van Osch, Gerjo J. V. M.
A1  - van Leeuwen, Johannes P. T. M.
A1  - van Driel, Marjolein
T1  - Follistatin Effects in Migration, Vascularization, and Osteogenesis in vitro and Bone Repair in vivo
JF  - Frontiers in Bioengineering and Biotechnology
N2  - The use of biomaterials and signaling molecules to induce bone formation is a promising approach in the field of bone tissue engineering. Follistatin (FST) is a glycoprotein able to bind irreversibly to activin A, a protein that has been reported to inhibit bone formation. We investigated the effect of FST in critical processes for bone repair, such as cell recruitment, osteogenesis and vascularization, and ultimately its use for bone tissue engineering. In vitro, FST promoted mesenchymal stem cell (MSC) and endothelial cell (EC) migration as well as essential steps in the formation and expansion of the vasculature such as EC tube-formation and sprouting. FST did not enhance osteogenic differentiation of MSCs, but increased committed osteoblast mineralization. In vivo, FST was loaded in an in situ gelling formulation made by alginate and recombinant collagen-based peptide microspheres and implanted in a rat calvarial defect model. Two FST variants (FST288 and FST315) with major differences in their affinity to cell-surface proteoglycans, which may influence their effect upon in vivo bone repair, were tested. In vitro, most of the loaded FST315 was released over 4 weeks, contrary to FST288, which was mostly retained in the biomaterial. However, none of the FST variants improved in vivo bone healing compared to control. These results demonstrate that FST enhances crucial processes needed for bone repair. Further studies need to investigate the optimal FST carrier for bone regeneration.
KW  - follistatin 315 (FST315)
KW  - follistatin 288 (FST288)
KW  - migration
KW  - vascularization
KW  - osteogenesis
KW  - injectable in situ gelling slow release system
KW  - bone tissue engineering
KW  - regenerative medicine
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227617
VL  - 7
ER  -